Long-term outcome of hemizygous and heterozygous carriers of a germline GATA1G208R mutation
| Autor: | Christian Flotho, Ulrich Dührsen, Günter Brittinger, Erika König, Christian P. Kratz, Thomas Lauenstein, Martin Bommer, Hermann Heimpel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Heterozygote Adolescent Gout Biology Kidney Article Germline mutation Mutation Carrier Paraparesis Pregnancy Internal medicine medicine Humans Erythropoiesis Family GATA1 Transcription Factor Child Skewed X-inactivation Germ-Line Mutation Megakaryocytopoiesis Anemia Dyserythropoietic Congenital Hemizygote Hematology General Medicine Middle Aged medicine.disease Extramedullary hematopoiesis Pedigree Abortion Spontaneous medicine.anatomical_structure Endocrinology Hematopoiesis Extramedullary Female Bone marrow Gastrointestinal Hemorrhage Dyserythropoietic anemia |
| Popis: | The transcriptional regulator GATA1 is crucially involved in megakaryocytopoiesis and erythropoiesis. Mutations of the gene which is located on the X chromosome have been associated with platelet and red blood cell abnormalities. We identified a family with a GATA1 G208R mutation in whom a low male birth rate and frequent miscarriages among heterozygous females suggested increased fetal death in male hemizygotes. Female mutation carriers had normal or near normal hemoglobin levels and platelet counts ranging from normal to severely reduced, probably reflecting skewed X chromosome inactivation. Platelets were dimorphous, and thrombocytopenia was associated with erythroblastosis. The only living male mutation carrier had severe macrothrombocytopenia with life-threatening bleeding episodes, moderate to severe anemia, eosinopenia, skeletal abnormalities, and abundant extramedullary hematopoiesis. Long-term sequelae in the 50-year-old patient included unilateral nephrectomy following misinterpretation of paraspinal hematopoiesis as renal cancer, spinal stenosis which was possibly favored by progressive bone marrow expansion, and severe secondary gout. |
| Databáze: | OpenAIRE |
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